1. Field of the Invention
This invention relates to a new and useful drug delivery device. Specifically, the invention concerns a drug delivery device for administering a drug to achieve a local or systemic physiological or pharmacological effect wherein the device comprises a plurality of projections for penetrating the stratum corneum of the epidermis, and a reservoir containing a drug in immediate proximity with the projections for supplying a drug for percutaneous administration through the stratum corneum penetrated by the projections.
2. Description of the Prior Art
A long felt need existed in the medical art, prior to this invention, for a drug delivery device for use in the percutaneous administration of a drug. This need existed because the art lacked a device for percutaneously administering a drug at a programmed rate of drug administration to achieve a particular drug level in the circulatory system for a preselected period of time, and also because the art lacked a device for percutaneously administering a drug that essentially overcame the skin' natural barrier to penetration by bacterial, chemical or other external substances. The skin'S barrier to penetration stems from both its morphological and marcomolecular organization
Morphologically, the composite epithelial layer of the skin, also called epidermis, is the part of the skin endowed with the barrier against penetration, and it consists of four layers. These layers are an outermost layer called stratum corneum and three underlying layers called stratum granulosum, stratum malpighii and stratum germinativum. The stratum corneum is a heterogenous layer of flattened, relatively dry, keratinised cells with a dense underlying layer commonly called the horny layer. In the past, it was generally held that this horny layer acted as the barrier to the penetration of external substances into the body. J. Invest. Dermat., Vol 50, pages 19 to 26, 1968. Now, it is generally held that the whole stratum corneum and not a discrete cellular layer functions as a barrier to the penetration of substances into the body. The whole stratum corneum is held to be a barrier because of a chemical keratin-phospholipid complex that exists in the stratum corneum and acts along with the horny layer as a barrier to the penetration of substances into the body. For this invention, the whole stratum corneum is considered as the natural barrier to penetration. J. Invest. Dermat., Vol 50, pages 371 to 379, 1968; and, ibid, Vol 56, pages 72 to 78, 1971.
The stratum corneum, which is about 15 microns thick when dry and about 48 microns thick when fully hydrated, acts as a barrier for an extremely large variety of compounds. The barrier holds for compounds with large molecular volumes, for compounds substituted with functional groups, for small soluble molecules, for non-electroytes, and the like. J. Invest. Dermat., Vol 52, pages 63 to 70, 1969. Once a compound is made to pass through the stratum corneum, for example, by surgically stripping the stratum corneum, there is no major hindrance to penetration of the remaining epidermal layers or the dermis. After this, the compound enters into the circulation via the capillaries. Progress in the Biological Sciences in Relation to Dermatology, 2nd Ed., pages 245, 1964, Univ. Press, Cambridge; and, J. of Drug and Cosmetic Ind., Vol 108, No. 2, pages 36 to 39 and 152 to 154, 1971.
In view of the above presentation, once a drug has penetrated through the stratum corneum, with the aid of the drug delivery device of the invention, penetration through the remaining layers of the skin proceeds readily. Absorption of a drug into the stratum corneum with no further penetration is considered retention and not percutaneous penetration. The passage of the drug into local or systemic circulation is considered as a further or continuing result of percutaneous penetration of drug administered according to this invention. As used herein, the term "percutaneous" means penetration through the skin to the local or systemic circulatory system by puncturing, scraping, or cutting the stratum corneum but not puncturing, scraping, or cutting to a substantial extent, the interior layers of the skin.
Those skilled in the art will appreciate that drug retention, as discussed above, is usually achieved by using devices known as scarifiers or vaccinating instruments. These instruments and their results are significantly different from the drug delivery device of this invention and its results. For example, scarifiers and like instruments usually scarify, that is, they scratch or make small cuts or an area for vaccination as reported in Webster's Seventh New Collegiate Dictionary, 1969, page 769; and, Stedman's Medical Dictionary, 1966, page 1728. These instruments are used by the medical art for a single, quick, application of a massive dose of vaccine and they are not used by the medical arts as a drug delivery device for the controlled and prolonged administration of effective amounts of a drug for local therapy or systemic therapy. Representative of prior art sacrifiers and vaccinating instruments are U.S. Pat. No. 2,947,787 which discloses a bubble containing a biological fluid and an injector with prongs of 1 to 10 millimeters in length for rupturing the bubble and for applying a single, topical application of the fluid; U.S. Pat. No. 2,893,392, disclosing an envelope containing a biological liquid and an injector with prongs of 1 to 5 millimeters for penetrating the envelope, scarifying the skin and applying a single dose of vaccine thereto; U.S. Pat. No. Re. 25,637 illustrating a capsule and a serrated scarifier for dispensing a vaccine and scratching the skin with the same instrumentality; and U.S. Pat. Nos. 3,123,212; 2,522,306; 3,351,059, and the like that disclose scarifiers with prongs of at least 150 microns in length for making superficial incision in the skin for applying a vaccine thereto. Thus, as taught by the prior art, these instruments have a single, immediate use while the drug delivery device of this invention can be designed for the continual, prolonged, controlled release of a drug to produce a local or systemic effect. Also, the projections of the drug delivery device of this invention are designed to penetrate the stratum corneum for the administration of a drug without contacting the body nerves for achieving an essentially painless drug administration.